Glycopyrrolate, the active pharmaceutical ingredient in Robinul® tablets, Robinul® Forte tablets and Robinul® injection, is a quaternary ammonium compound having the chemical name 3-[(cyclopentylhydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide. Glycopyrrolate is an anticholinergic and antispasmodic that inhibits gastrointestinal nerve receptor sites that stimulate both the secretion of stomach acid and smooth muscle activity in the digestive tract. Accordingly, it diminishes the volume and free acidity of gastric secretions and controls excessive pharyngeal, tracheal, and bronchial secretions.
Glycopyrrolate is indicated for use as adjunctive therapy in the treatment of peptic ulcer. See PHYSICIANS' DESK REFERENCE (57th ed., Medical Economics Co., 2003). The most frequent adverse reactions to glycopyrrolate include those that are common to anticholinergics generally including, for example, xerostomia, decreased sweating, urinary hesitancy and retention, blurred vision, tachycardia, palpitations, headaches, dizziness, nausea, vomiting, nervousness, and other reactions.
Pharmacokinetic studies have not previously been conducted to evaluate the effect of food on the pharmacokinetics of glycopyrrolate. It is desirable to increase the oral bioavailability of a drug substance, such as glycopyrrolate, to increase the extent of the therapeutic effect on the user. In general, food has a variable effect on the bioavailability of an active agent. Drug-food interactions may result in reduced, delayed or increased systemic drug availability. See, e.g., Clin Pharmacokinet 1984 Sep–Oct; 9(5):404–34. Food may interact with a coadministered drug at the following phases: (i) before and during gastrointestinal absorption; (ii) during distribution; (iii) during metabolism; and (iv) during elimination. See Clin Pharmacokinet 1999 September; 37(2):213–55. For some drugs such as, for example, nefazodone and troglitazone, bioavailability increases with food. See Clin Pharmacokinet 1997 October; 33(4):260–75; Clin Pharmacokinet 1999 August; 37(2):91–104.
There remains a need for a method of treatment of peptic ulcer and other gastrointestinal disorders using glycopyrrolate that has increased oral bioavailability and, thus, improved efficacy following administration to human patients.